LONP2

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0006625 protein targeting to peroxisome	IBA GO_REF:0000033	ACCEPT	Summary: IBA annotation based on phylogenetic inference. LONP2 facilitates protein targeting to peroxisomes by processing PTS2-containing proteins after their import into the peroxisomal matrix. The deep research confirms LONP2 plays a direct role in peroxisomal protein import regulation through involvement in processing PTS2-containing proteins. Reason: LONP2's role in protein targeting to peroxisome is well-established. UniProt states LONP2 is "necessary for type 2 peroxisome targeting signal (PTS2)-containing protein processing and facilitates peroxisome matrix protein import." This is a core function of the protein. Supporting Evidence: file:human/LONP2/LONP2-deep-research-perplexity.md LONP2 plays a direct role in peroxisomal protein import regulation through its involvement in processing peroxisomal targeting signal 2 (PTS2) containing proteins
GO:0005782 peroxisomal matrix	IBA GO_REF:0000033	ACCEPT	Summary: IBA annotation for peroxisomal matrix localization. LONP2 is well-established as a peroxisomal matrix protein, specifically concentrated in the dense crystalline core of the organelle where oxidative stress is highest. Reason: Core localization. UniProt states subcellular location as "Peroxisome matrix" with evidence from multiple publications (PMID:14561759, PMID:18281296, PMID:22002062). The protein contains a C-terminal PTS1 (SKL motif) for peroxisomal targeting. Supporting Evidence: file:human/LONP2/LONP2-deep-research-perplexity.md this protease not only localizes to the peroxisomal matrix but specifically concentrates within the dense crystalline core of the organelle
GO:0016485 protein processing	IBA GO_REF:0000033	ACCEPT	Summary: IBA annotation for protein processing. LONP2 processes PTS2-containing proteins and degrades self-processed forms of TYSND1, which itself processes peroxisomal beta-oxidation enzymes including ACOX1. Reason: Core biological process. UniProt states LONP2 is "necessary for type 2 peroxisome targeting signal (PTS2)-containing protein processing." The degradation of TYSND1 cleavage products represents a key protein processing function. Supporting Evidence: file:human/LONP2/LONP2-deep-research-perplexity.md Tysnd1 undergoes self-cleavage to generate inactive fragments, which are subsequently degraded by LONP2
GO:0000166 nucleotide binding	IEA GO_REF:0000043	ACCEPT	Summary: IEA annotation based on UniProt keyword mapping. LONP2 contains an AAA+ ATPase domain with Walker A and B motifs that bind and hydrolyze ATP. Reason: Accurate but general annotation. The protein has an established ATP binding site (residues 375-382) and ATP binding is essential for its proteolytic activity. This is subsumed by the more specific GO:0005524 ATP binding annotation but is not incorrect. Supporting Evidence: file:human/LONP2/LONP2-deep-research-perplexity.md The central ATPase domain contains the canonical Walker A and B motifs characteristic of AAA+ (ATPases Associated with diverse cellular Activities) proteases
GO:0004176 ATP-dependent peptidase activity	IEA GO_REF:0000120	ACCEPT	Summary: IEA annotation from InterPro domain analysis. LONP2 is definitively an ATP-dependent peptidase - ATP hydrolysis is absolutely essential for its proteolytic activity. Reason: Core molecular function. UniProt catalytic activity states "Hydrolysis of proteins in presence of ATP" (EC 3.4.21.53). Deep research confirms ATP hydrolysis is absolutely essential for proteolytic activity. Supporting Evidence: file:human/LONP2/LONP2-deep-research-perplexity.md A fundamental characteristic of LONP2 as an ATP-dependent enzyme is that ATP hydrolysis is absolutely essential for proteolytic activity
GO:0004252 serine-type endopeptidase activity	IEA GO_REF:0000120	ACCEPT	Summary: IEA annotation from InterPro and EC number mapping. LONP2 is a serine protease with a Ser-Lys catalytic dyad in its C-terminal proteolytic domain. Reason: Core molecular function. UniProt assigns EC 3.4.21.53 (Lon protease) and documents the active site residues Ser-743 and Lys-786. Mutagenesis of Ser-743 to Ala reduces degradation of TYSND1 and causes loss of ACOX1 processing. Supporting Evidence: file:human/LONP2/LONP2-deep-research-perplexity.md The carboxyl-terminal proteolytic domain contains the catalytically active serine-lysine dyad responsible for peptide bond cleavage
GO:0005524 ATP binding	IEA GO_REF:0000120	ACCEPT	Summary: IEA annotation based on domain analysis. LONP2 has a defined ATP binding site (residues 375-382) within its AAA+ ATPase domain. Reason: Core molecular function. ATP binding is required for the proteolytic activity of LONP2. UniProt documents the ATP binding site at residues 375-382 with ligand ChEBI:30616. Supporting Evidence: file:human/LONP2/LONP2-deep-research-perplexity.md These Walker motifs are conserved three-dimensional protein structures that mediate ATP binding and hydrolysis
GO:0005782 peroxisomal matrix	IEA GO_REF:0000120	ACCEPT	Summary: IEA annotation for peroxisomal matrix localization, duplicating the IBA annotation. Based on UniRule transfer from characterized orthologs. Reason: Correct localization. Duplicates the IBA annotation but with different evidence basis. Both are acceptable as they reflect the same biological truth from independent evidence sources. Supporting Evidence: file:human/LONP2/LONP2-deep-research-perplexity.md LONP2 contains a C-terminal peroxisomal targeting signal (PTS1) consisting of the characteristic SKL (serine-lysine-leucine) or variant motif that directs the protein to peroxisomes
GO:0006508 proteolysis	IEA GO_REF:0000120	ACCEPT	Summary: IEA annotation for proteolysis. LONP2 is a protease that degrades misfolded and oxidatively damaged proteins in the peroxisomal matrix. Reason: Core biological process. LONP2 is definitively a protease and proteolysis is its primary function. This general term accurately captures the proteolytic activity, though more specific terms also apply. Supporting Evidence: file:human/LONP2/LONP2-deep-research-perplexity.md LONP2 represents a multifunctional ATP-dependent serine protease specialized for maintaining proteostasis in the peroxisomal matrix through selective degradation of oxidatively damaged and misfolded proteins
GO:0006515 protein quality control for misfolded or incompletely synthesized proteins	IEA GO_REF:0000120	ACCEPT	Summary: IEA annotation for protein quality control. LONP2's primary function is degrading misfolded and oxidatively damaged proteins in the peroxisomal matrix. The 2023 Yamashita study directly demonstrated peroxisomal proteotoxic stress (TYSND1 substrate accumulation) upon acute LONP2 depletion in mammalian cells. Reason: Core biological process. UniProt states LONP2 "mediates the selective degradation of misfolded and unassembled polypeptides in the peroxisomal matrix." This is a defining function of peroxisomal Lon proteases, with both protease and chaperone activities supporting peroxisomal proteostasis. Supporting Evidence: file:human/LONP2/LONP2-deep-research-perplexity.md LONP2 is an ATP-dependent serine protease that serves as a critical regulator of peroxisomal protein quality control through selective degradation of misfolded and oxidatively damaged proteins file:human/LONP2/LONP2-deep-research-falcon.md A 2023 primary study frames LONP2 as a peroxisomal protease/chaperone and demonstrates that acute LONP2 silencing triggers “early” peroxisomal proteotoxic stress: accumulation of the reported substrate TYSND1 PMID:37736739 Lon peptidases act as both a chaperone and an ATP dependent protease responsible for the degradation and turnover of oxidized proteins in bacteria, mitochondria, peroxisomes and chloroplasts
GO:0008233 peptidase activity	IEA GO_REF:0000043	ACCEPT	Summary: IEA annotation based on UniProt keyword mapping. General peptidase activity term that is a parent of the more specific serine-type endopeptidase. Reason: Accurate but general. LONP2 is a peptidase (EC 3.4.21.53). More specific terms (ATP-dependent peptidase activity, serine-type endopeptidase activity) are also annotated and provide better specificity. Supporting Evidence: file:human/LONP2/LONP2-deep-research-perplexity.md LONP2 functions as an ATP-dependent protease that mediates the selective degradation of misfolded and unassembled polypeptides
GO:0008236 serine-type peptidase activity	IEA GO_REF:0000043	ACCEPT	Summary: IEA annotation for serine-type peptidase activity. LONP2 uses a Ser-Lys catalytic dyad for peptide bond cleavage. Reason: Accurate. LONP2 is a serine protease with active site Ser-743. This is a parent term of serine-type endopeptidase activity which is also annotated. Supporting Evidence: file:human/LONP2/LONP2-deep-research-perplexity.md The carboxyl-terminal proteolytic domain contains the catalytically active serine-lysine dyad responsible for peptide bond cleavage
GO:0016485 protein processing	IEA GO_REF:0000104	ACCEPT	Summary: IEA annotation for protein processing based on UniRule. Duplicates the IBA annotation with different evidence basis. Reason: Correct. Protein processing is a core function of LONP2, particularly processing of PTS2-containing proteins. This duplicates the IBA annotation but represents independent computational evidence. Supporting Evidence: file:human/LONP2/LONP2-deep-research-perplexity.md LONP2 plays a direct role in peroxisomal protein import regulation through its involvement in processing peroxisomal targeting signal 2 (PTS2) containing proteins
GO:0016558 protein import into peroxisome matrix	IEA GO_REF:0000104	ACCEPT	Summary: IEA annotation for protein import into peroxisome matrix. LONP2 facilitates import by processing PTS2-containing proteins after translocation, and Yamashita et al. 2023 directly demonstrated that LONP2 silencing impairs PTS1 luminal protein (CFP-SKL) import while sparing membrane protein (PEX3-YFP) import. Reason: This annotation reflects LONP2's role in facilitating peroxisomal protein import through processing of PTS2-containing proteins. UniProt states it "facilitates peroxisome matrix protein import." Yamashita 2023 directly confirmed a selective luminal-import defect upon LONP2 knockdown. Supporting Evidence: file:human/LONP2/LONP2-deep-research-perplexity.md The functional significance of this PTS2-associated proteolysis appears to facilitate accumulation of processed proteins within the peroxisomal matrix file:human/LONP2/LONP2-deep-research-falcon.md In mammalian cells, LONP2 silencing causes failure of matrix import for a canonical luminal reporter (CFP-SKL, a PTS1-containing protein), while import of a membrane marker (PEX3-YFP) is maintained PMID:37736739 CFP-SKL was efficiently targeted to peroxisomes in control cells, but no longer imported into peroxisomes in LONP2-silenced COS-7 cells
GO:0016787 hydrolase activity	IEA GO_REF:0000043	ACCEPT	Summary: IEA annotation for general hydrolase activity. LONP2 is an ATP-dependent hydrolase that cleaves peptide bonds. Reason: Accurate but very general. LONP2 catalyzes hydrolysis of peptide bonds. More specific terms are also annotated. Supporting Evidence: file:human/LONP2/LONP2-deep-research-perplexity.md LONP2 functions as an ATP-dependent protease that mediates the selective degradation of misfolded and unassembled polypeptides
GO:0016887 ATP hydrolysis activity	IEA GO_REF:0000120	ACCEPT	Summary: IEA annotation for ATP hydrolysis activity based on InterPro AAA+ domain. LONP2 hydrolyzes ATP to power substrate unfolding and translocation. Reason: Core molecular function. ATP hydrolysis is essential for LONP2's proteolytic activity. The ATPase domain contains Walker A/B motifs for ATP hydrolysis. Supporting Evidence: file:human/LONP2/LONP2-deep-research-perplexity.md These Walker motifs are conserved three-dimensional protein structures that mediate ATP binding and hydrolysis, allowing LONP2 to harness the energy of ATP to power substrate unfolding and translocation
GO:0030163 protein catabolic process	IEA GO_REF:0000002	ACCEPT	Summary: IEA annotation from InterPro for protein catabolic process. LONP2 degrades proteins as part of peroxisomal quality control. Reason: Accurate. LONP2 mediates protein degradation/catabolism in the peroxisomal matrix. This is a general term that correctly describes LONP2's proteolytic degradation function. Supporting Evidence: file:human/LONP2/LONP2-deep-research-perplexity.md LONP2 functions as an ATP-dependent protease that mediates the selective degradation of misfolded and unassembled polypeptides within the peroxisomal matrix
GO:0005515 protein binding	IPI PMID:27173435 An organelle-specific protein landscape identifies novel dis...	REMOVE	Summary: IPI annotation for protein binding from organelle proteomics study. This is from a high-throughput interactome study. Reason: Generic protein binding is uninformative for a protease that must bind substrates. More specific binding annotations (enzyme binding, protease binding) are available. High-throughput interactome studies often capture non-specific interactions. Supporting Evidence: file:human/LONP2/LONP2-deep-research-perplexity.md Experimentally identified substrates of LONP2 in mammalian cells include the serine protease trypsin domain-containing 1 (Tysnd1) PMID:27173435 An organelle-specific protein landscape identifies novel diseases and molecular mechanisms.
GO:0005515 protein binding	IPI PMID:28514442 Architecture of the human interactome defines protein commun...	REMOVE	Summary: IPI annotation for protein binding from interactome architecture study. High-throughput interaction data. Reason: Generic protein binding is uninformative. The publication is a high-throughput interactome study. More specific binding terms (enzyme binding, protease binding) already capture the functionally relevant interactions. Supporting Evidence: file:human/LONP2/LONP2-deep-research-perplexity.md Experimentally identified substrates of LONP2 in mammalian cells include the serine protease trypsin domain-containing 1 (Tysnd1), which itself is responsible for processing peroxisomal enzymes including acyl-coenzyme A oxidase 1 (ACOX1) PMID:28514442 Architecture of the human interactome defines protein communities and disease networks.
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	REMOVE	Summary: IPI annotation for protein binding from binary interactome reference map. High-throughput interaction data. Reason: Generic protein binding is uninformative for annotation purposes. This high-throughput study does not provide functional insight beyond what more specific binding annotations capture. Supporting Evidence: file:human/LONP2/LONP2-deep-research-perplexity.md The relationship between LONP2 and Tysnd1 is particularly notable PMID:32296183 Apr 8. A reference map of the human binary protein interactome.
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	REMOVE	Summary: IPI annotation for protein binding from dual proteome interactome study. High-throughput interaction data. Reason: Generic protein binding from high-throughput study is uninformative. More specific binding annotations are available for LONP2's functionally relevant interactions. Supporting Evidence: file:human/LONP2/LONP2-deep-research-perplexity.md Experimentally identified substrates of LONP2 in mammalian cells include the serine protease trypsin domain-containing 1 (Tysnd1) PMID:33961781 2021 May 6. Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
GO:0005634 nucleus	IEA GO_REF:0000107	REMOVE	Summary: IEA annotation for nuclear localization based on Ensembl ortholog transfer. This appears to be based on mouse ortholog data. Reason: LONP2 is specifically a peroxisomal protein with a C-terminal PTS1 targeting signal (SKL motif). All experimental evidence points to exclusive peroxisomal matrix localization. UniProt states "Peroxisome matrix" without any nuclear annotation. This IEA appears to be an erroneous transfer and contradicts the established subcellular localization. Supporting Evidence: file:human/LONP2/LONP2-deep-research-perplexity.md LONP2 contains a C-terminal peroxisomal targeting signal (PTS1) consisting of the characteristic SKL (serine-lysine-leucine) or variant motif that directs the protein to peroxisomes
GO:0005737 cytoplasm	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: IEA annotation for cytoplasm localization. LONP2 is synthesized in the cytoplasm before import into peroxisomes. Reason: LONP2 is synthesized on free ribosomes in the cytoplasm before being targeted to peroxisomes. This represents a transit location, not the functional localization. The peroxisomal matrix is where LONP2 performs its functions. Supporting Evidence: file:human/LONP2/LONP2-deep-research-perplexity.md The protein is encoded by the LONP2 gene from the nuclear genome on chromosome 16 and is synthesized on free ribosomes in the cytoplasm before being targeted to the peroxisomal compartment
GO:0005777 peroxisome	IEA GO_REF:0000107	ACCEPT	Summary: IEA annotation for peroxisome localization based on Ensembl ortholog transfer. Correct localization but less specific than peroxisomal matrix. Reason: Correct. LONP2 localizes to peroxisomes, specifically the peroxisomal matrix. This general term is a parent of the more specific peroxisomal matrix annotation. Supporting Evidence: file:human/LONP2/LONP2-deep-research-perplexity.md LONP2 contains a C-terminal peroxisomal targeting signal (PTS1) consisting of the characteristic SKL (serine-lysine-leucine) or variant motif that directs the protein to peroxisomes
GO:0005782 peroxisomal matrix	TAS Reactome:R-HSA-9033235	ACCEPT	Summary: TAS annotation for peroxisomal matrix from Reactome pathway annotation. Reactome pathway R-HSA-9033235 is "Cargo of PEX5S,L translocates from the cytosol to the peroxisomal matrix". Reason: Correct core localization. LONP2 is a cargo protein that is imported into the peroxisomal matrix via the PEX5 receptor. This is consistent with experimental evidence. Supporting Evidence: file:human/LONP2/LONP2-deep-research-perplexity.md The PTS1 sequence is recognized by the peroxisomal import receptor Pex5, which shuttles LONP2 across the peroxisomal membrane into the matrix
GO:0005829 cytosol	TAS Reactome:R-HSA-9033235	KEEP AS NON CORE	Summary: TAS annotation for cytosol from Reactome. This reflects the cytosolic location of newly synthesized LONP2 before import into peroxisomes. Reason: LONP2 is synthesized in the cytosol before import into peroxisomes. This represents a transit location for the protein before it reaches its functional destination in the peroxisomal matrix. Supporting Evidence: file:human/LONP2/LONP2-deep-research-perplexity.md The protein is encoded by the LONP2 gene from the nuclear genome on chromosome 16 and is synthesized on free ribosomes in the cytoplasm before being targeted to the peroxisomal compartment
GO:0005829 cytosol	TAS Reactome:R-HSA-9033236	KEEP AS NON CORE	Summary: TAS annotation for cytosol from Reactome pathway R-HSA-9033236 "PEX5S,L:Cargo binds PEX13:PEX14:PEX2:PEX10:PEX12 (Docking and Translocation Module)". Reason: Duplicates annotation from R-HSA-9033235. Cytosol is the transit location where LONP2 binds PEX5 before import into peroxisomes. Supporting Evidence: file:human/LONP2/LONP2-deep-research-perplexity.md The protein is encoded by the LONP2 gene from the nuclear genome on chromosome 16 and is synthesized on free ribosomes in the cytoplasm
GO:0016020 membrane	HDA PMID:19946888 Defining the membrane proteome of NK cells.	REMOVE	Summary: HDA annotation for membrane from high-throughput mass spectrometry proteomics study of NK cell membrane proteome. This is a general membrane term. Reason: LONP2 is a soluble peroxisomal matrix protein, not a membrane protein. The detection in a membrane proteomics study likely represents contamination or association with peroxisomal membranes during sample preparation. All evidence indicates LONP2 localizes to the peroxisomal matrix, not to membranes. Supporting Evidence: file:human/LONP2/LONP2-deep-research-perplexity.md this protease not only localizes to the peroxisomal matrix but specifically concentrates within the dense crystalline core of the organelle PMID:19946888 Defining the membrane proteome of NK cells.
GO:0006625 protein targeting to peroxisome	IMP PMID:18281296 Contribution of peroxisome-specific isoform of Lon protease ...	ACCEPT	Summary: IMP annotation from Omi et al. 2008 showing LONP2 contributes to sorting PTS1 proteins to peroxisomes through mutant phenotype analysis. Reason: Core function with experimental evidence. The paper demonstrates that LONP2 contributes to peroxisomal protein targeting through mutagenesis studies. UniProt cites this paper for the S743A and PTS1 deletion mutant phenotypes. Supporting Evidence: file:human/LONP2/LONP2-deep-research-perplexity.md LONP2 plays a direct role in peroxisomal protein import regulation through its involvement in processing peroxisomal targeting signal 2 (PTS2) containing proteins PMID:18281296 Contribution of peroxisome-specific isoform of Lon protease in sorting PTS1 proteins to peroxisomes.
GO:0008233 peptidase activity	IDA PMID:18281296 Contribution of peroxisome-specific isoform of Lon protease ...	ACCEPT	Summary: IDA annotation for peptidase activity from direct experimental assay in Omi et al. 2008. Reason: Core molecular function with direct experimental evidence. The paper provides direct assay evidence for LONP2 peptidase activity. Supporting Evidence: file:human/LONP2/LONP2-deep-research-perplexity.md LONP2 functions as an ATP-dependent protease that mediates the selective degradation of misfolded and unassembled polypeptides within the peroxisomal matrix PMID:18281296 Contribution of peroxisome-specific isoform of Lon protease in sorting PTS1 proteins to peroxisomes.
GO:0016485 protein processing	IMP PMID:18281296 Contribution of peroxisome-specific isoform of Lon protease ...	ACCEPT	Summary: IMP annotation for protein processing from mutant phenotype analysis in Omi et al. 2008. Reason: Core biological process with experimental evidence. Mutagenesis of the catalytic serine (S743A) causes loss of ACOX1 processing, demonstrating LONP2's role in protein processing. Supporting Evidence: file:human/LONP2/LONP2-deep-research-perplexity.md Tysnd1 undergoes self-cleavage to generate inactive fragments, which are subsequently degraded by LONP2 PMID:18281296 Contribution of peroxisome-specific isoform of Lon protease in sorting PTS1 proteins to peroxisomes.
GO:0002020 protease binding	IPI PMID:22002062 Two proteases, trypsin domain-containing 1 (Tysnd1) and pero...	ACCEPT	Summary: IPI annotation for protease binding from Okumoto et al. 2011 showing interaction with TYSND1. Independently corroborated by Yamashita 2023, which observed accumulation of LONP2-substrate TYSND1 self-cleavage products upon LONP2 knockdown in mammalian cells. Reason: Functional binding annotation with experimental evidence. LONP2 interacts with TYSND1, a trypsin-domain containing protease. This interaction is functionally significant for coordinating peroxisomal protein processing and fatty acid beta-oxidation regulation. Supporting Evidence: file:human/LONP2/LONP2-deep-research-perplexity.md Experimentally identified substrates of LONP2 in mammalian cells include the serine protease trypsin domain-containing 1 (Tysnd1) PMID:22002062 2011 Oct 14. Two proteases, trypsin domain-containing 1 (Tysnd1) and peroxisomal lon protease (PsLon), cooperatively regulate fatty acid β-oxidation in peroxisomal matrix. PMID:37736739 Immunoblotting of LONP2-silenced cells after 6 days revealed an accumulation of the auto-cleaved products of the protease TYSND1, products established as LONP2 substrates
GO:0031998 regulation of fatty acid beta-oxidation	IMP PMID:22002062 Two proteases, trypsin domain-containing 1 (Tysnd1) and pero...	ACCEPT	Summary: IMP annotation from Okumoto et al. 2011 demonstrating LONP2's role in regulating fatty acid beta-oxidation through TYSND1 degradation. Reason: Core biological process with experimental evidence. UniProt states LONP2 "may indirectly regulate peroxisomal fatty acid beta-oxidation through degradation of the self-processed forms of TYSND1." The 2011 study provides direct evidence for this function. Supporting Evidence: file:human/LONP2/LONP2-deep-research-perplexity.md LONP2 maintains the functionality of this critical metabolic pathway by proteolytically degrading peroxisomal proteins damaged by the oxidative stress inherent to beta-oxidation PMID:22002062 2011 Oct 14. Two proteases, trypsin domain-containing 1 (Tysnd1) and peroxisomal lon protease (PsLon), cooperatively regulate fatty acid β-oxidation in peroxisomal matrix.
GO:0005777 peroxisome	IDA PMID:22002062 Two proteases, trypsin domain-containing 1 (Tysnd1) and pero...	ACCEPT	Summary: IDA annotation for peroxisome localization from direct experimental observation in Okumoto et al. 2011. Reason: Core localization with direct experimental evidence. Multiple studies confirm peroxisomal localization through immunofluorescence and subcellular fractionation. Supporting Evidence: file:human/LONP2/LONP2-deep-research-perplexity.md this protease not only localizes to the peroxisomal matrix but specifically concentrates within the dense crystalline core of the organelle PMID:22002062 2011 Oct 14. Two proteases, trypsin domain-containing 1 (Tysnd1) and peroxisomal lon protease (PsLon), cooperatively regulate fatty acid β-oxidation in peroxisomal matrix.
GO:0019899 enzyme binding	IPI PMID:18281296 Contribution of peroxisome-specific isoform of Lon protease ...	ACCEPT	Summary: IPI annotation for enzyme binding from Omi et al. 2008 showing interaction with ACOX1 (peroxisomal acyl-coenzyme A oxidase 1). Reason: Functional binding annotation with experimental evidence. LONP2 interacts with ACOX1 and other beta-oxidation enzymes including ABCD3 and ACAA1 (per UniProt interaction data from this paper). Supporting Evidence: file:human/LONP2/LONP2-deep-research-perplexity.md Tysnd1, which itself is responsible for processing peroxisomal enzymes including acyl-coenzyme A oxidase 1 (ACOX1) PMID:18281296 Contribution of peroxisome-specific isoform of Lon protease in sorting PTS1 proteins to peroxisomes.
GO:0005515 protein binding	IPI PMID:18281296 Contribution of peroxisome-specific isoform of Lon protease ...	MODIFY	Summary: IPI annotation for protein binding from Omi et al. 2008. The specific interacting partner is ABCD3 (ATP-binding cassette sub-family D member 3). Reason: Generic protein binding is uninformative. The interaction with ABCD3 (a peroxisomal membrane transporter) could be annotated more specifically. The enzyme binding annotation from the same paper better captures the functionally relevant interactions. Proposed replacements: enzyme binding Supporting Evidence: file:human/LONP2/LONP2-deep-research-perplexity.md Experimentally identified substrates of LONP2 in mammalian cells include the serine protease trypsin domain-containing 1 (Tysnd1) PMID:18281296 Contribution of peroxisome-specific isoform of Lon protease in sorting PTS1 proteins to peroxisomes.
GO:0005777 peroxisome	IDA PMID:18281296 Contribution of peroxisome-specific isoform of Lon protease ...	ACCEPT	Summary: IDA annotation for peroxisome localization from Omi et al. 2008 using immunofluorescence microscopy. Reason: Core localization with direct experimental evidence. Duplicates IDA evidence from PMID:22002062 but represents independent experimental confirmation. Supporting Evidence: file:human/LONP2/LONP2-deep-research-perplexity.md this protease not only localizes to the peroxisomal matrix but specifically concentrates within the dense crystalline core of the organelle PMID:18281296 Contribution of peroxisome-specific isoform of Lon protease in sorting PTS1 proteins to peroxisomes.
GO:0007031 peroxisome organization	NAS PMID:14561759 Proteomic analysis of rat liver peroxisome - presence of per...	ACCEPT	Summary: NAS annotation for peroxisome organization from Kikuchi et al. 2004, the paper that first identified peroxisomal Lon protease in rat liver. Yamashita 2023 directly demonstrates peroxisome remodeling (fewer, enlarged and elongated peroxisomes) upon LONP2 silencing in mammalian cells, strengthening this annotation. Reason: LONP2 contributes to peroxisome organization through its protein quality control function. Loss of LONP2 leads to accumulation of protein aggregates and peroxisome enlargement in model organisms; new mammalian data (Yamashita 2023) directly support reduced peroxisome number and increased size upon LONP2 depletion. Supporting Evidence: file:human/LONP2/LONP2-deep-research-perplexity.md Studies in the fungus Phaffia chrysogenum harboring deletion mutations of the peroxisomal Lon gene (pln) demonstrated marked increases in the accumulation of electron-dense protein aggregates, accompanied by increased peroxisome number and enlargement file:human/LONP2/LONP2-deep-research-falcon.md Upon LONP2 depletion, peroxisomes become fewer and enlarged/elongated, and matrix import fails for a luminal reporter, establishing LONP2 as a determinant of peroxisome structural/functional homeostasis. PMID:37736739 Confocal microscopy demonstrated that peroxisomes were less abundant, but individual peroxisomes were elongated and enlarged in both cell lines PMID:14561759 Oct 15. Proteomic analysis of rat liver peroxisome: presence of peroxisome-specific isozyme of Lon protease.
GO:0005777 peroxisome	IDA PMID:14561759 Proteomic analysis of rat liver peroxisome - presence of per...	ACCEPT	Summary: IDA annotation for peroxisome localization from the original proteomic identification of peroxisomal Lon in rat liver (Kikuchi et al. 2004). Reason: Core localization with direct experimental evidence from proteomic analysis of rat liver peroxisomes. This was the foundational study identifying peroxisome-specific Lon protease. Supporting Evidence: file:human/LONP2/LONP2-deep-research-perplexity.md Ultracentrifugation studies using antibodies raised against the C-terminal region of LONP2 have demonstrated that this protease not only localizes to the peroxisomal matrix PMID:14561759 Oct 15. Proteomic analysis of rat liver peroxisome: presence of peroxisome-specific isozyme of Lon protease.

Gene Description

Existing Annotations Review

Core Functions

LONP2's primary molecular function is ATP-dependent proteolysis. It uses ATP hydrolysis to power substrate unfolding and translocation into the proteolytic chamber where the Ser-Lys catalytic dyad cleaves peptide bonds. ATP is absolutely essential for proteolytic activity.

References

Deep Research

Falcon

OpenAI

Perplexity

Perplexity

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